An interim analysis of a phase 2 trial evaluating oral nalbuphine extended release for treating chronic cough in idiopathic pulmonary fibrosis

Abstract

<b>Background:</b> Cough is a major cause of morbidity in idiopathic pulmonary fibrosis (IPF), which lacks effective therapies. Mixed opioid agonists/antagonists can reduce chronic cough by pharmacologically acting on the opioid system potentially at both peripheral and central nervous system levels. <b>Aim:</b> Report an interim analysis of a phase 2 trial with an extended-release (ER) oral form of the dual-acting ƙ opioid receptor agonist/µ opioid receptor antagonist nalbuphine (NAL) evaluated for IPF-related chronic cough to establish proof-of-concept. <b>Methods:</b> A randomised, double-blind, placebo (PBO)-controlled, crossover trial with two 22-day treatment periods (1: NAL ER-PBO; 2: PBO-NAL ER) separated by a 2-week washout was conducted. NAL ER 27 mg once daily was titrated up to 162 mg twice daily at day 16. Adults diagnosed with definite/probable IPF using international criteria and chronic cough for &gt;8 weeks were enrolled. The primary endpoint was percent change from baseline in hourly daytime cough frequency using an objective digital monitor (VitaloJAK) analysed with a mixed-effects model. <b>Results:</b> Of 45 screened subjects, 26 comprised the period 1 full analysis set. Subjects were primarily male with a mean age &gt;70 years and cough frequency of 31/hr. A 77.3% reduction from baseline to day 22 in hourly cough frequency for NAL ER (51.6% PBO-adjusted difference; p&lt;.0001) was observed. No new safety signals were identified. <b>Conclusion:</b> In this interim analysis of phase 2 data, NAL ER is the first therapy to show a significant reduction in IPF-related hourly daytime chronic cough frequency.